期刊
ANESTHESIOLOGY
卷 113, 期 1, 页码 58-73出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/ALN.0b013e3181dc1b5b
关键词
-
资金
- Nancy Paduano Investment Retirement Fund, New York, New York
- C.V. Starr Foundation, New York, New York
- Department of Anesthesiology, Weill Medical College of Cornell University, New York, New York
Background: The ultra-short-acting neuromuscular blocker gantacurium is chemically degraded in vitro by rapid adduction of L-cysteine to its central olefinic double bond. Preliminary data have suggested that exogenous (intravenous) L-cysteine abolishes gantacurium blockade. Two new analogues of gantacurium (CW 002 and CW 011) have been synthesized to undergo slower L-cysteine adduction, yielding intermediate duration. L-Cysteine adduction to and antagonism of these novel agents is further defined herein. Methods: Comparative reaction half-time for L-cysteine adduction in vitro of the three compounds was determined by high-performance liquid chromatography. ED95 for twitch inhibition in monkeys under isoflurane was calculated, and duration at similar to 4-5 x ED95 was correlated with reaction half-time for adduction. Speed of L-cysteine antagonism was contrasted with anticholinesterase reversal. Potencies of CW 002 and its adduction product were compared to provide a basis for L-cysteine antagonism. Results: Rate of L-cysteine adduction in vitro (reaction half-time) was 11.4 and 13.7 min for CW 002 and CW 011 versus 0.2 min for gantacurium, and was inversely related to duration of block (P < 0.0001). CW 002 and CW 011 were 3 x longer acting than gantacurium (28.1 and 33.3 min vs. 10.4 min), but only half the duration of cisatracurium. The adduct of CW 002 was similar to 70 x less potent than CW 002. L-Cysteine (10-50 mg/kg intravenously) given 1 min after approximately 4-5 x ED95 doses of all the three compounds abolished block within 2-3 min. Conclusions: L-Cysteine adduction occurs at different rates by design in olefinic isoquinolinium diester neuromuscular blockers, yielding corresponding durations of action. Antagonism by exogenous L-cysteine is superior to anticholinesterases, inducing inactivation of the active molecules to restore function rapidly at any time.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据